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1、外泌体在肿瘤研究中的应用,癌细胞作为受体,经典文献:,1.DendriticcellexosomesdirectlykilltumorcellsandactivatenaturalkillercellsviaTNFsuperfamilyligands;2.Aberrantlowexpressionofp85instromalfibroblastspromotesbreastcancercellmetastasisthroughexosome-mediatedparacrineWnt10b;3.ExosomeTransferfromStromaltoBreastCancerCellsRegula
2、tesTherapyResistancePathways;4.MicroRNAsTransferfromHumanMacrophagestoHepato-CarcinomaCellsandInhibitProliferation;,癌细胞作为供体,例:,1.CancerExosomesPerformCell-IndependentMicroRNABiogenesisandPromoteTumorigenesis;2.ExosomesSecretedunderHypoxiaEnhanceInvasivenessandStemnessofProstateCancerCellsbyTargeting
3、AdherensJunctionMolecules;3.CancerExosomesTriggerFibroblasttoMyofibroblastDifferentiation;4.Exosomederivedfromepigallocatechingallatetreatedbreastcancercellssuppressestumorgrowthbyinhibitingtumor-associatedmacrophageinfiltrationandM2polarization;5.Humantumorvirusutilizesexosomesforintercellularcommu
4、nication;6.MurineMammaryCarcinomaExosomesPromoteTumorGrowthbySuppressionofNKCellFunction;,应用:Thenovelbiomarkers,例:,1.ClinicalImpactofSerumExosomalMicroRNA-21AsaClinicalBiomarkerinHumanEsophagealSquamousCellCarcinoma;2.Glypican-1identifiescancerexosomesanddetectsearlypancreaticcancer;3.Double-strande
5、dDNAinexosomesanovelbiomarkerincancerdetection;4.ExosomallongnoncodingRNACRNDE-hasanovelserum-basedbiomarkerfordiagnosisandprognosisofcolorectalcancer;,应用:Therapy,例:,1.ExosomesderivedfromIL-12-anchoredrenalcancercellsincreaseinductionofspecificantitumorresponseinvitro;2.SystemicallyInjectedExosomesT
6、argetedtoEGFRDeliverAntitumorMicroRNAtoBreastCancerCells;3.AphaseIstudyofdexosomeimmunotherapyinpatientswithadvancednon-smallcelllungcancer;4.Dendriticcell-derivedexosomesasmaintenanceimmunotherapyafterfirstlinechemotherapyinNSCLC;,思路:,1.测序(蛋白/mRNA/miRNA/lncRNA/circRNA)2.测序(蛋白/mRNA/miRNA/lncRNA/circ
7、RNA)+临床验证3.功能+测序(蛋白/mRNA/miRNA/lncRNA/circRNA)4.功能+简单信号通路5.功能+蛋白/mRNA/miRNA/lncRNA/circRNA+下游机制6.功能+蛋白/mRNA/miRNA/lncRNA/circRNA+上游调控7.功能+蛋白/mRNA/miRNA/lncRNA/circRNA+上游调控+下游机制8.创新性想法提出,例:,1.ProteomicAnalysisofExosome-likeVesiclesDerivedfromBreastCancerCells,ANTICANCERRESEARCH.2.ClinicalImpactofSeru
8、mExosomalMicroRNA-21AsaClinicalBiomarkerinHumanEsophagealSquamousCellCarcinoma,Cancer.3.Exosome-TransmittedlncARSRPromotesSunitinibResistanceinRenalCancerbyActingasaCompetingEndogenousRNA,Cacnercell.4.Pancreaticcancerexosomesinitiatepre-metastaticnicheformationintheliver,NATURECELLBIOLOGY;5.Tumourex
9、osomeintegrinsdetermineorganotropicmetastasis,Nature;,经典文献:126-year-old“seed-and-soil”hypothesis,FuturemetastaticsitesUptakeExosomes,Exosomesredirectmetastaticdistribution,Organ-specifictumourexosomesinteractwithResidentcells.,Exosomesredirectmetastaticdistribution,ExosomalITGsdetermineorganotropism
10、,ExosomalITGsasorganotropismbiomarkers,胰腺癌早期诊断:Glypican-1identifiescancerexosomesanddetectsearlypancreaticcancer,nature,2015,GPC1isaspecificmarkerofcancerexosomes,GPC11circulatingexosomesareacancerbiomarker.GPC11crExoscontainoncogenicKRASG12D.,GPC11crExosdetectearlypancreaticcancer,LevelsofcirculatingGPC11Exosomesinformpancreaticcancerresectionoutcome,Elisa,GPC11crExosdetectearlyPanINlesions.,谢谢!,